Minocycline May Improve Stroke Outcomes Out to 24 Hours

October 1, 2007 — Results of a randomized open-label trial suggest that the use of minocycline 6 to 24 hours after an acute ischemic stroke is associated with significantly improved clinical outcomes.

“The improvement was already apparent within a week of the stroke,” said study author Yair Lampl, MD, from the Edith Wolfson Medical Center and Tel Aviv University, in Israel, in a statement from the American Academy of Neurology. “This is exciting because many people who have had a stroke cannot be treated if they don’t get to the hospital within 3 hours after symptoms start, which is the time frame for currently available treatments.”

However, he added, “while these are promising results, a much larger, closed-label study is needed to confirm our findings.”

Their report appears in the October 2 issue of Neurology.

I’m not a basic scientist, and had no idea minocycline is being studied for neuroprotection. A medline search yielded more than 100 papers citing studies of minocycline and neuroprotection from all sorts of insults. More on that later.

The proposed mechanism of benefit is thought to relate not to its antibiotic action but to its anti-inflammatory effects, a reduction in microglial activation, matrix metalloproteinase reduction, nitric oxide production, or inhibition of apoptotic cell death, they note.

…The primary outcome was change from baseline to day 90 on the National Institutes of Health Stroke Scale (NIHSS) with minocycline treatment vs placebo;

…Results showed that NIHSS and mRS scores were significantly lower and BI scores significantly higher in patients who received minocycline than controls, with significant differences (P < .0001) for each of these tests found at days 7, 30, and 90.

NIHSS Scores by Treatment Group

End Point

Minocycline

Placebo

Mean NIHSS score on admission

7.5 + 3.2

7.6 + 3.8

Mean NIHSS score at 90 days

1.6 + 1.9

6.5 + 3.8

If this pans out, it’ll be a cheap and easy treatment for stroke (unless you’re allergic to the tetracycline class).

But, remember all those papers studying minocycline and neuroprotection?

Asked for comment by Medscape Neurology & Neurosurgery, Philip Gorelick, MD, from the University of Illinois College of Medicine at Chicago, said this study by Lampl and colleagues “provides an exciting possibility for neuroprotection” and that “minocycline [is] a multipotential neuroprotectant in acute ischemic stroke. These early-phase study results suggest that this agent may be beneficial.

“It is too early to conclude, however, that the agent is efficacious in acute ischemic stroke; a large-scale study will be needed to prove the point,” he adds. “As everyone knows, all prior studies have failed to definitively prove that neuroprotection in acute ischemic stroke is safe and effective. We look forward to the results of further testing of this agent in the hopes of finally finding a neuroprotectant that works.”

It’s not standard of care now; more studies are needed, but we’d all like a ‘magic bullet’ to aid in stroke recovery.

As an aside, I’ve been verycritical of some of the lay reporting about tPA, and I’d like to emphasize here that my objection to tPA has been to an outsized risk of adverse outcomes even when used as judiciously as possible. This doesn’t mean I’m fatalistic about stroke patients or their care: like every working EM doc I want to see all of them dance and sing their way out of the hospital. I’m down on tPA (somewhat) but not the patients.